Optically clear polymer compositions containing an interpenetrant

ABSTRACT

Disclosed are optically clear xerogel polymer compositions containing an interpenetrant.

This application is a continuation of U.S. Ser. No. 08/338,744 filed onNov. 9, 1994, now U.S. Pat. No. 5,482,981.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention is directed to optically clear xerogel polymercompositions containing an interpenetrant. These compositions arecharacterized by the presence of hydroxyl functionalities which areblocked with a removable blocking group which, after removal of theblocking groups and hydration of the composition, will have a watercontent of at least 10 weight percent and preferably from about 35 toabout 70 weight percent and a modulus of at least about 2 Mdyne/cm².

This invention is further directed to methods for the preparation ofoptically clear hydrogel polymer compositions containing hydroxylfunctionality and an interpenetrant.

2. State of the Art

Hydrogel polymer compositions and the use of these compositions inophthalmic devices, especially contact lenses, are well known in theart. Such hydrogel polymer compositions are typically manufactured ascopolymeric systems, optionally cross-linked which are formed in thexerogel state where they are hard materials. This xerogel, in thepresence of water or other water containing solvent, hydrates andundergoes a change so that it attains the hydrogel state. Uponhydration, the resulting polymer composition contains water and,accordingly, becomes softer and more pliable as compared to the polymercomposition prior to hydration. The degree of softness and pliability isrelated to the amount of water incorporated into the polymer compositionafter hydration. Additionally, contact lenses derived from polymercompositions having large amounts of water provide greater wearercomfort and higher oxygen permeability. Accordingly, the art hasgenerally been directed to the incorporation of large amounts of waterinto such polymer compositions.

However, notwithstanding the desirability of incorporating large amountsof water into hydrogel polymer compositions, one problem typicallyencountered is that as the water contents increases, the structuralrigidity of the polymer composition, as measured by its modulus,decreases and can reach a point where the structural rigidity is lessthan desirable. Accordingly, the hydrogel polymer composition istypically formulated to balance the need for a large water content andfor a suitable modulus and the values achieved for both parameters isoften compromised from ideal values.

In regard to the above, it is known in the art that an interpenetrantincorporated into a polymer composition increases the structuralrigidity of the composition thereby providing a means to obtain adesired level of water content while retaining suitable structuralrigidity.

However, a problem is encountered in the area of ophthalmic devices whena large amount of an interpenetrant, i.e., greater than about 1.5 weightpercent (based on the dry weight of the polymer composition), isincorporated into a hydrogel polymer composition comprising hydroxylgroups. Specifically, it has been found that the use of such a largeamount of interpenetrant in such hydrogel polymer compositions rendersthe resulting composition optically opaque. Without being limited to anytheory, it is believed that the hydroxyl comprising polymer compositionshave poor solubility for the interpenetrant and, accordingly, opticalopacity for the resulting composition arises from phase separation ofthe interpenetrant from the polymer. In any event, optically opaquematerials cannot be used in ophthalmic devices because optical clarityis an overriding criticality in these devices.

In one embodiment, the art has circumvented this problem by includinglarge quantities of an organic solvent (e.g., about 80-95 weight percentor more), such as dimethyl sulfoxide (DMSO), with an interpenetrantchemically modified to include a reactive vinyl group. See, for example,European Patent Application Publication No. 0 456 611. The organicsolvent acts to solubilize the interpenetrant as well as themonomer/polymer composition and the reactive vinyl group acts tocovalently incorporate the interpenetrant into the polymer backboneduring polymerization.

After polymerization, the resulting polymer is solvated (i.e., not axerogel). The inclusion of large amounts of solvent in the polymers viasuch methods complicates the manufacturing process of ophthalmic devicesfrom hydrogel materials because such materials are typically cast orformed in the xerogel state, and once solvated, become soft and pliablewhich makes machining the solvated materials difficult. Accordingly, thefinal shape and other physical characteristics of the polymeric articleare preferably formed during the xerogel state, i.e., in the absence ofsignificant amounts of any solvent. The inclusion of large amounts ofsolvent in the prior art methods for forming an optically clear polymercomposition containing an interpenetrant will, however, preclude theformation of such a xerogel composition.

In view of the above, the art has heretofore been seeking, withoutsuccess, an optically clear xerogel polymer composition comprisinghydroxyl groups on the polymer and having incorporated therein at leastabout 1.5 weight percent of an interpenetrant.

SUMMARY OF THE INVENTION

This invention is directed, in part, to optically clear xerogel polymercompositions comprising a polymer and at least about 1.5 weight percentof an interpenetrant (based on the weight of the xerogel) wherein thepolymer comprises blocked hydroxyl functional groups wherein theblocking groups are removable. The xerogel polymer compositions arefurther characterized as forming, upon deblocking and hydration, ahydrogel polymer composition having a water content of at least 10weight percent and preferably from about 35 to about 70 weight percentand a modulus of at least about 2 Mdynes/cm².

Accordingly, in one of its composition aspects, this invention isdirected to an optically clear xerogel polymer composition comprising:

a polymer comprising blocked hydroxyl functional groups, and

at least about 1.5 weight percent of an interpenetrant based on thetotal weight of the xerogel polymer composition

wherein said composition has a sufficient optical clarity to permit thepassage of at least 80% of visible light through a 0.1 millimeter (mm)thick sample of the composition.

In a preferred embodiment, the polymer composition described above iscross-linked. In a further preferred embodiment, the polymercomposition, after deblocking and hydration, has a water content of atleast 10 weight percent and even more preferably from about 35 to about70 weight percent water based on the total weight of the hydratedhydrogel polymer composition and a modulus of at least about 2Mdynes/cm².

In a further preferred embodiment, the hydrated hydrogel polymercomposition prepared from the xerogel polymer described above has amodulus of from 2 to 50 Mdyne/cm², more preferably 5 to 30 Mdyne/cm² andstill more preferably greater than about 12 Mdyne/cm², a percentelongation of greater than about 100% and more preferably greater thanabout 175% and an oxygen permeability of greater than about 10 Dk unitsand more preferably greater than about 18 Dk units.

In a still further preferred embodiment, the hydrated hydrogel polymercomposition has a water content of from about 45 to 70% and morepreferably about 50%.

This invention is also directed, in part, to the unexpected discoverythat the preparation of such optically clear hydrogel polymercompositions can be obtained by placing a removable block group on thehydroxyl groups of the monomer component(s) prior to polymerization andincorporation of an interpenetrant therein. After polymerization andinterpenetrant incorporation, the blocking groups are removed and thexerogel polymer composition hydrated to provide for an optically clearhydrogel polymer composition.

Accordingly, in one of its method aspects, this invention is directed toa method for the preparation of an optically clear xerogel polymercomposition comprising a polymer comprising hydroxyl functionalitieswhich functionalities are blocked with a removable blocking group, andat least about 1.5 weight percent of an interpenetrant based on thetotal weight of the xerogel polymer composition which method comprises:

(a) selecting a monomer composition wherein each component thereofcomprises a reactive vinyl functionality and at least one of thecomponents of the composition comprises at least one hydroxyl functionalgroup;

(b) blocking the hydroxyl functionalities on each of the hydroxylcontaining monomer components selected in (a) above with a removableblocking group;

(c) combining said monomer composition with at least 1.5 weight percentof an interpenetrant based on the total weight of the composition; and

(d) polymerizing the composition produced in (c) above to provide for anoptically clear xerogel polymer composition.

In a preferred embodiment, the method described above further comprises:

(e) removing the blocking groups from said hydroxyl groups; and

(f) hydrating the composition produced in (e) above.

In another preferred embodiment, an effective amount of a cross-linkeris incorporated into the monomer composition prior to polymerizationprocedure (d).

DETAILED DESCRIPTION OF THE INVENTION

As noted above, this invention is directed, in part, to optically clearxerogel polymer compositions containing an interpenetrant and methodsfor preparing such compositions. However, prior to discussing thisinvention in further detail, the following terms will first be defined:

The term "hydrogel polymer composition" refers to the polymercompositions described herein which, after polymer formation, arehydratable when treated with water and, accordingly, can incorporatewater into the polymeric matrix without itself dissolving in water.Typically, water incorporation is effected by making the polymercomposition in a water solution for a sufficient period so as toincorporate at least 10 weight percent water and preferably from about35 to about 70 weight percent water, and more preferably about 50 weightpercent water, into the polymer composition based on the total weight ofthe polymer composition.

The term "xerogel polymer composition" refers to the composition formedin the absence of large quantities of added solvent wherein any solventin the polymer composition is typically less than about 5 weight percentof the total composition and more preferably less than about 2 weightpercent of the total composition.

The term "removable blocking group" refers to any group which when boundto one or more hydroxyl groups prevents reactions from occurring atthese hydroxyl groups and which protecting groups can be selectivelyremoved by conventional chemical and/or enzymatic procedures toreestablish the hydroxyl group. The particular removable blocking groupemployed is not critical and preferred removable hydroxyl blockinggroups include conventional substituents such as benzyl, benzoyl,acetyl, chloroacetyl, trichloroacetyl, fluoroacetyl, trifluoroacetyl,t-butylbiphenylsilyl and any other group that can be introduced onto ahydroxyl functionality and later selectively removed by conventionalmethods in mild conditions compatible with the nature of the product. Ina particularly preferred embodiment, the removable blocking group is asolvolyzable blocking group.

In another preferred embodiment, the removable blocking group isselected such that upon hydration and removal of the removable blockinggroup, little or no dimensional change occurs in the polymer. Morepreferably, the extent of dimensional change, as measured by change inpercent expansion, is controlled to less than about ±25% and even morepreferably to less than about ±10%.

The term "solvolyzable" or "solvolyzable blocking groups" refers togroups capable of cleavage into a carboxyl containing compound and analcohol, in the presence of a nucleophile, for example, a hydroxyl ionin water or a weak base such as ammonia or an organic amine or a C₁ to aC₄ alcohol. Solvolyzable blocking groups include acyl and haloacylblocking groups of from 2 to 8 carbon atoms as well as a haloacylblocking group of the formula X₃ CC(O)O-- wherein each X isindependently selected from the group consisting of fluoro and chloro.Preferably, the solvolyzable groups are capable of being solvolyzedunder mild solvolysis conditions such as in aqueous solutions of a pH offrom greater than 7 to less than about 12 and a temperature of less thanabout 60° C. Such solvolyzable leaving groups are well known in the artand a list of such solvolyzable leaving groups is described in, forexample, European Patent Application Publication No. 0 495 603 A1, U.S.Pat. No. 4,638,040 and U.S. Pat. No. 5,362,768 all of which areincorporated herein by reference in their entirety.

The term "interpenetrant" refers to structurally rigid, high molecularweight materials which are soluble, at the levels employed, in at leastone of the components utilized in preparing the polymer compositionsdescribed herein. Such interpenetrants are well known in the an andinclude, by way of example, siloxane, polyurethane, cellulose acetatebutyrate, cellulose, hydroxyethyl cellulose and hydroxypropyl cellulose,hydroxyethyl hydroxypropyl cellulose, mixtures of interpenetrants, aswell as interpenetrants chemically modified to include a polymerizablegroup such as vinyl groups, epoxide groups, isocyanates, etc. (see, forexample European Patent Application Publication No. 0 456 611) and thelike. Such interpenetrants are either commercially available or can beprepared by an recognized techniques from commercially availablestarting materials. The particular interpenetrant employed is notcritical. Preferably, the interpenetrant has a molecular weight of fromabout 1,000 to about 50,000,000 and more preferably from about 5,000 toabout 500,000.

Interpenetrants are considered as structurally rigid if 1.5% of theinterpenetrant increases the modulus of a polymer composition by atleast 1 Mdyne/cm² as compared to the same polymer composition in theabsence of the interpenetrant.

The term "compatible ethylenically unsaturated monomers free of hydroxylgroups" refers to monomers which do not contain either hydroxyl groupsor blocked hydroxyl groups; which can participate in polymer formationwith a monomer containing hydroxyl groups blocked with a removableblocking group; and which, when so incorporated into the polymercomposition provide for a polymer composition which, after solvolysisand hydration, is suitable for use in ophthalmic devices, i.e., thehydrogel polymer is clear so as to transmit visible light. Suitablecompatible ethylenically unsaturated monomers free of hydroxyl groupsinclude, by way of example, methyl acrylate, methyl methacrylate,trifluoromethyl methacrylate, trifiuoromethyl acrylate,2',2',2'-trifluoroethyl methacrylate, 2',2',2'-trifluoroethyl acrylate,ethyl methacrylate, ethyl acrylate, styrene, and the like. Suchmaterials are well known in the art and are either commerciallyavailable or can be prepared by methods known per se in the art.

Preferably, the compatible ethylenically unsaturated monomer free ofhydroxyl groups solubilizes, in whole or in part, the interpenetrantemployed. A particularly preferred combination of a compatibleethylenically unsaturated monomer free of hydroxyl groups and aninterpenetrant is methyl methacrylate and cellulose acetate butyrate.Another preferred compatible ethylenically unsaturated monomer free ofhydroxyl groups is phenoxyethyl methacrylate which also solubilizescellulose acetate butyrate, although less efficiently than methylmethacrylate.

The term "cross-linking agent" refers to a monomer containing at leasttwo reactive groups capable of forming covalent linkages with reactivegroups found on at least one of the monomers used to prepare the polymercompositions described herein. Suitable reactive groups include, forexample, vinyl groups which can participate in the polymerizationreaction. The reactive groups are typically substituents on a suitablebackbone such as a polyoxyalkylene backbone (including halogenatedderivatives thereof), a polyalkylene backbone, a glycol backbone, aglycerol backbone, a polyester backbone, a polyamide backbone, polyureabackbone, a polycarbonate backbone, and the like.

Cross-linking agents for use in the preferred compositions describedherein are well known in the art and the particular cross-linking agentemployed is not critical. Preferably, however, the reactive vinyl groupis attached to the backbone of the cross-linking agent via an ester bondsuch as that found in acrylate and methacrylate derivatives such asurethane diacrylate, urethane dimethacrylate, ethylene glycoldiacrylate, ethylene glycol dimethacrylate, polyoxyethylene diacrylate,polyoxyethylene dimethacrylate, and the like. However, other suitablevinyl compounds include, by way of example, di- and higher- vinylcarbonates, di- and higher-vinyl amides (e.g., CH₂ ═CH--C(O)NHCH₂ CH₂NHC(O)CH═CH₂), and the like.

Preferred cross-linking agents include, by way of example, ethyleneglycol dimethacrylate, ethylene glycol diacrylate, diethylene glycoldimethacrylate, diethylene glycol diacrylate, triethylene glycoldimethacrylate, triethylene glycol diacrylate, tetradecaethylene glycoldimethacrylate, tetradecaethylene glycol diacrylate, allyl methacrylate,allyl acrylate, trimethylol-propane trimethacrylate, trimethylolpropanetriacrylate, 1,3-butanediol dimethacrylate, 1,3-butanediol diacrylate,1,4-butanediol dimethacrylate, 1,4-butanediol diacrylate, 1,6-hexanedioldimethacrylate, 1,6-hexanediol diacrylate, 1,9-nonanedioldimethacrylate, 1,9-nonanediol diacrylate, 1,10-decanedioldimethacrylate, 1,10-decanediol diacrylate, neopentyl glycoldimethacrylate, neopentyl glycol diacrylate,2,2'bis[p-(γ-methacryloxy-β-hydroxypropoxy)phenyl]propane,pentaerythritol triacrylate, pentaerythritol trimethacrylate,pentaerythritol tetraacrylate, pentaerythritol tetramethacrylate,1,4-cyclohexanediol diacrylate, 1,4-cyclohexanediol dimethacrylate,ethoxylated bis-phenol-A-diacrylate, ethoxylatedbis-phenol-A-dimethacrylate, bis-phenol-A-dimethacrylate,bis-phenol-A-diacrylate, N,N'-methylenebisacrylamide, as well asdifunctional macromers having a molecular weight of from about 1,000 toabout 1,000,000. Such materials are well known in the art and are eithercommercially available or can be prepared by methods known per se in theart.

The cross-linking agent preferably has at least 2 and more preferablyfrom 2 to about 6 vinyl functionalities and preferably has a numberaverage molecular weight of from about 100 to about 2,500 (except forthe macromers described above). More preferably, the vinylfunctionalities are acrylate or methacrylate groups attached to apolyoxyalkylene backbone (including halogenated derivatives thereof), apolyalkylene backbone, a glycol backbone, a glyceroI backbone, apolyester backbone, or a polycarbonate backbone.

Formulations

The polymer compositions described herein are prepared by firstpreparing a suitable formulation containing the requisite components andthen polymerizing the formulation. Specifically, the formulationcomprises a monomer composition and an interpenetrant.

The monomer composition comprises at least one monomer componentcomprising a reactive vinyl functionality and at least one hydroxylfunctional group wherein the hydroxyl groups are blocked with aremovable blocking group. Suitable hydroxyl monomer components (prior toblocking) include hydroxyethyl methacrylate (HEMA), hydroxyethylacrylate, glycidyl methacrylate, glycidyl acrylate, hydroxypropylmethacrylate, hydroxypropyl acrylate, butanediol monomethacrylate,mixtures of such components, and the like. Suitable blocking groupsinclude, by way of example only, benzyl, benzoyl, acetyl, chloroacetyl,trichloroacetyl, fluoroacetyl, trifluoroacetyl, t-butyl-biphenylsilylgroups, and the like. When the monomer component contains more than onehydroxyl group, e.g., glycidyl methacrylate, the removable blockinggroups employed therewith may be the same or different groups but, forease of synthesis, are preferably the same.

The monomer composition can optionally contain one or more compatibleethylenically unsaturated monomers free of hydroxyl groups. When themonomer composition does contains such ethylenically unsaturatedmonomers free of hydroxyl groups, the composition preferably comprisessufficient hydroxyl containing monomers such that the resulting hydrogelpolymer composition will absorb at least 10 weight percent and morepreferably from 35 to about 70 weight percent water. In a particularlypreferred embodiment, the monomer composition comprises at least about20 weight percent of monomer component(s) comprising a reactive vinylfunctionality having at least one hydroxyl functional group wherein thehydroxyl groups are blocked with a removable blocking group and morepreferably from about 50 to about 100 weight percent based on the totalweight of the monomer composition and still more preferably from about80 to 100 weight percent.

The formulation also contains an interpenetrant which is employed in theamount of at least about 1.5 weight percent based on the total weight ofthe formulation (in the absence of any water) and preferably from about5 to about 60 weight percent and more preferably from about 5 to about30 weight percent. The use of higher concentrations of interpenetrantmay decrease the water content of the resulting hydrated polymercomposition. The specific amount of interpenetrant employed is selectedso that the hydrogel polymer composition has a modulus of at least 2Mdynes/cm², preferably 2 to 50 Mdynes/cm² and more preferably 2 to 30Mdynes/cm².

The compositions of this invention are preferably cross-linked and,accordingly, one of the components of a preferred formulation is across-linking agent. When employed, the cross-linking agent is employedin an amount sufficient to provide a cross-linked product but preferablyis employed in an amount of from about 0.1 to about 30 weight percent,more preferably from about 0.1 to about 5 weight percent and still morepreferably from about 0.2 to about 3 weight percent based on the totalweight of the formulation. The use of higher amounts of cross-linkerappears to correlate to polymer compositions having a higher modulus butlower water content and a lower percent elongation.

The formulation can optionally contain one or more additional componentssuch as initiators, colorants, etc. which are conventionally employed inthe art.

These formulations as well as the reagents employed to prepare theseformulations are preferably stored and formulated in containers whichprevent premature polymerization of one or more of the reagents. Forexample, the use of amber bottles for storing reagents inhibitsphoto-induced polymerization.

Methodology

The formulations described above are readily polymerized by conventionaltechniques such as thermal, UV, γ irradiation, or electron beam inducedpolymerization to provide for the polymer composition. For example,thermal induced polymerization can be achieved by combining a suitablepolymerization initiator into the mixture of monomers under an inertatmosphere (e.g., argon) and maintaining the mixture at an elevatedtemperature of from about 20° C. to about 75° C. for a period of timefrom about 1 to about 48 hours.

Ultraviolet (UV) induced polymerization can be achieved by combining asuitable polymerization initiator into the mixture of monomers under aninert atmosphere (e.g., argon) and maintaining the mixture under asuitable UV source. Preferably, UV induced polymerization is conductedat ambient conditions for a period of from about 5 minutes to 24 hours.

Suitable polymerization initiators are well known in the art includingthermal initiators such as t-butyl peroxy pivalate (TBPP), t-butylperoxy neodecanoate (TBPN), benzoyl peroxide, methyl ethyl ketoneperoxide, diisopropyl peroxycarbonate and the like and UV initiatorssuch as benzophenone, Darocur 1173 (available from Ciba Geigy, Ardsley,N.Y., USA), bis-azoisobutyronitrile and the like.

The particular thermal or UV initiator employed is not critical andsufficient initiator is employed to catalyze the polymerizationreaction. Preferably, the initiator is employed at up to about 1 weightpercent based on the total weight of the composition.

Polymerization achieved by either electron beams or γ irradiation doesnot require the use of an initiator and the formulation to bepolymerized is merely exposed to the electron beam or γ irradiationusing conventional methods.

Polymerization is typically conducted in a manner so as to facilitatemanufacture of the finished contact lens. For example, polymerizationcan be conducted in molds which correspond to the structure of thecontact lens. Alternatively, polymerization can be conducted so as toform a polymer rod which can be machined (lathed) to provide contactlenses of suitable dimensions. In this latter embodiment, polymerizationcan be conducted in a silylated glass test tube and afterpolymerization, the test tube is broken to provide for the polymericrod. The rod, in the form of the xerogel, can be machined, for example,lathed, cut, milled, and consequently, the rod can be made into contactlenses by cutting small cylinders or buttons from the rod and subsequentlathing. In still another alternative embodiment, polymerization can beconducted in a base curve mold to provide a button suitable for forminga contact lens.

In any event, after polymerization, a post-curing procedure isoptionally employed to complete the polymerization process whichpost-curing step typically increases the hardness of the polymer. Thepost-curing procedure can comprise heating the polymer to a temperatureof from about 60° C. to 120° C. for a period of from about 2 to about 24hours. Alternatively, the post-curing step can employ γ irradiation offrom about 0.1 to about 5 Mrad. Combinations of these two procedures canalso be employed.

The polymer compositions described above, preferably in the contact lensforms described, are then subjected to removal of the removable blockinggroup and hydrolysis. The conditions for removal of the removableblocking group are dependent, of course, on the blocking group employedand it is well within the skill of the art to select the appropriateconditions relative to the blocking group employed. Either during orafter removal of the removable blocking group, the composition is thensubjected to conventional hydration to provide for the hydrated form ofthe composition.

In a particularly preferred embodiment, the removable blocking group isa solvolyzable blocking group and solvolysis of the blocking groups andhydration of the polymer composition occurs simultaneously. Solvolysisis preferably conducted by suspending the contact lens in an aqueoussolution in the presence of a nucleophile, for example, a hydroxyl ionin water or a weak base such as ammonia or an organic amine or a C₁ to aC₄ alcohol. Preferably, the solvolyzable groups are capable of beingsolvolyzed under mild solvolysis conditions such as in aqueous solutionsof a pH of from greater than 7 to less than about 12 and a temperatureof from about 10° C. to about 60° C.

Under these conditions, hydration of the polymer material also occurs.However, if desired, a separate hydration step can be employed.Hydration is continued until the polymer composition is fully hydratedwhich, in the present case, means that the water content of the hydrogelis from about 35 to about 70 weight percent.

In still another embodiment, water can be included in the polymerizationstep resulting in direct inclusion of water into the polymercomposition.

Utility

The xerogel polymer compositions described herein are suitable for usein medical and non-medical applications such as water absorbentmaterials useful in a variety of applications. After waterincorporation, the polymer compositions described herein areparticularly suitable for use in ophthalmic devices such as contactlenses providing requisite optical clarity, water content, highstrength, no deterioration over time, relatively slow release ofhydrated water upon exposure to air, and good optical propertiesincluding transparency.

When formed into contact lenses, the lenses are typically dimensioned tobe from about 0.02 to about 0.15 millimeters in thickness and preferablyfrom about 0.05 to about 0.10 millimeters in thickness (all thicknessesmeasured in the xerogel state).

The invention will now be illustrated by way of examples which areprovided for the purpose of illustration only and are not intended to belimiting in the present invention.

In the following examples, the following abbreviations represent thefollowing:

BPAGMA=bis-phenol-A 2-hydroxypropyl dimethacrylate

CAB=cellulose acetate butyrate

cm=centimeter

EGDMA=ethylene glycol dimethacrylate

EWC equilibrium water content

EX33=Esperox 33®(t-butylperoxyneodecanoate)

GMA=glycidyl methacrylate

HCEGMA=di-trichloroacetate ester of glyceryl methacrylate

LE=linear expansion

Mdynes=megadynes

min=minute

mm=millimeter

MMA methyl methacrylate

ppm=parts per million

EXAMPLES

In the examples set forth below, polymer compositional values are setforth for the Equilibrium Water Content ("EWC"), linear expansion andtensile properties (i.e., tensile strength, percent elongation andmodulus). Unless otherwise indicated, these values were determined asfollows:

Measurement of Equilibrium Water Content

Equilibrium Water Content (EWC) is determined by soaking the polymersamples in phosphate buffered saline solution for overnight. The samplesare removed, lightly blotted dry with a tissue and subsequently weighed.The hydrated samples are then placed in a vacuum oven at 60° C.overnight. The next day, the sample is reweighed. Equilibrium WaterContent is calculated using the following equation: ##EQU1## whereX=mass of hydrated polymer

Y=mass of dehydrated polymer

The EWC is sometimes referred to as the % water.

Measurement of Linear Expansion

Linear Expansion factor is determined by measuring the diameter of thexerogel polymer sample using the Nikon Profile Projector V-12 (availablefrom Nippon Kogaku K.K., Tokyo, Japan). The sample is then soakedovernight in phosphate buffered saline solution. The diameter issubsequently remeasured in phosphate buffered saline. Linear Expansionis calculated using the following equation: ##EQU2## where X=hydratedpolymer diameter

Y=Initial (dry) polymer diameter

Measurement of Tensile Properties

From a disc or a lens, a "dumb-bell" shaped specimen is cut. The sampleis inspected under a microscope for nicks and cuts. If these areobserved the sample is discarded. The thickness of the specimen is thenmeasured.

The sample is then placed between the clamps on an Instron tensiletester (available from Instron Corp., Canton, Massachusetts, USA) or anequivalent instrument. The initial grip separation used is 10 min. Thesample is placed under saline during measurement to prevent drying out.The experiment is then started with the cross-head speed set to 5mm/min. The Instron records the force required to pull on the sample asa function of cross-head displacement. This information is thenconverted into a stress-strain plot. The experiment continues until thesample breaks.

From the stress-strain plot are calculated the following:

Tensile strength: The maximum stress the sample can withstand beforebreaking.

Elongation: The amount of extension (expressed as a percent of originallength/grip separation) the sample undergoes before breaking

Modulus: Is the slope of the initial linear portion of the stress-straincurve.

The experiment is usually repeated with 5 samples from the same batch ofpolymer and the average and standard deviation are reported.

Comparative Example A and Example 1 below illustrate that blocking ofthe hydroxyl groups on the hydrophilic monomer is essential to preparingan optically clear xerogel polymer composition incorporating aninterpenetrant. Examples 2-3 exemplify that dimensional change occurringduring hydration can be controlled by selection of the polymercomposition relative to the removable blocking group. Examples 4-21illustrates further examples of polymer compositions of this invention.Example 22 illustrates enhancements in the amount of surface wettabilityachieved for molded ophthalmic devices from polymer compositions madevia the methods of this invention.

COMPARATIVE EXAMPLE A and EXAMPLE 1

Two xerogel polymer compositions were prepared by incorporating aninterpenetrant into the polymer composition which polymer compositionsin the hydrogel form contained hydroxyl functionality. Specifically, thefirst composition, Comparative Example A, was prepared such that thehydroxyl functionalities on the glycidyl methacrylate were not blockedwith a removable blocking group during polymer formation. Contrarily, inExample 1, the hydroxyl groups were blocked with a removable blockinggroup (i.e., as the trichloroacetate ester).

Specifically, the formulations for Comparative Example A and Example 1are as set forth in Table I below:

                  TABLE I                                                         ______________________________________                                               Monomer A                                                                              MMA/CAB.sup.1                                                                            BPAGMA.sup.2                                                                            EX33.sup.3                               ______________________________________                                        Example 1                                                                              HCEGMA.sup.4                                                                             2.19 g     0.274 g 0.107 g                                         (17.72 g)                                                            Comparative                                                                            GMA        4.38 g     0.548 g 0.107 g                                Example A                                                                              (12.58)                                                              ______________________________________                                         .sup.1 MMA/CAB = 30% wt:wt cellulose acetate butyrate in methyl               methacrylate                                                                  .sup.2 BPAGMA = bisphenol-A 2hydroxypropyl dimethacrylate (1:2 wt:wt          BPAGMA in DMSO)                                                               .sup.3 EX33 = Esperox 33                                                      .sup.4 HCEGMA = ditrichloroacetate ester of glyceryl methacrylate (stored     at least at -5° C. and preferably at -5° C.)               

These formulations were prepared by combining monomer A with both themethyl methacrylate/cellulose acetate butyrate composition and thecross-linker (BPAGMA). The composition was then mixed for 1 hour and,afterwards, degassed for 6 minutes. At this point, the initiator (EX33)was added to the composition and the formulation was again degassed,this time for 30 seconds. Degassing was conducted in order to avoidcontamination of the reaction vessel with oxygen which may have anadverse effect on the degree of polymerization. The resultingformulation was polymerized and cured in a programmable oven ramped at10° C./minute in the following manner to provide for a xerogel polymercomposition:

1) 40° C./2 hours

2) 55° C./2 hours

3) 70° C./2 hours

4) room temperature/4 hours

Afterwards, the xerogel polymers of Comparative Example A and Example 1were subjected to hydrolysis using a 5% solution of ammonium hydroxidewhich, in the case of Example 1, resulted both in removal of theblocking groups (via solvolysis) and hydration of the polymercomposition. The clarity/opaqueness of the resulting polymercompositions are set forth in Table II below:

                  TABLE II                                                        ______________________________________                                        POLYMER  OPTICAL PROPERTY                                                                              OPTICAL PROPERTY                                     OF       AS THE XEROGEL  AS THE HYDROGEL                                      ______________________________________                                        Comparative                                                                            optically opaque                                                                              optically opaque                                     Example A                                                                     Example 1                                                                              optically clear optically clear                                      ______________________________________                                    

Other physical properties for the polymer of Example 1 were determinedto be as follows: tensile strength=13.8±5.8 Mdynes/cm², percentelongation=211±89; modulus=22.1±12.3; and an EWC=52.3±2.5.

The results of this comparison establish that hydrogel polymercompositions containing an interpenetrant require the blocking of thehydroxyl groups on the monomers prior to polymerization in order toachieve optical clarity in either the xerogel or hydrogel composition.The physical properties of the polymer of Example 1 establish that thispolymer possesses tensile strength, percent elongation, modulus and EWCvalues suitable for use in ophthalmic devices.

EXAMPLES 2 and 3

The following examples illustrate that selection of the removableblocking group can be made to control of dimensional change arising fromhydrating the polymer composition. Specifically, the formulations forExamples 2 and 3 are as set forth in Table III below:

                  TABLE III                                                       ______________________________________                                        HCEGMA.sup.5  MMA/CAB.sup.6                                                                            BPAGMA.sup.7                                                                             EX33.sup.8                                ______________________________________                                        Example                                                                              94.24 wt % 5.236 wt %  0.523 wt %                                                                            0.4 wt %                                Example                                                                              89.22 wt % 9.345 wt % 0.9345 wt %                                                                            0.4 wt %                                3                                                                             ______________________________________                                         .sup.5 HCEGMA = ditrichloroacetate ester of glyceryl methacrylate (stored     at least at -5° C. and preferably at -5° C.)                    .sup.6 MMA/CAB = 30% wt:wt cellulose acetate butyrate in methyl               methacrylate                                                                  .sup.7 BPAGMA = bisphenol-A 2hydroxypropyl dimethacrylate (1:2 wt:wt          BPAGMA in DMSO)                                                               .sup.8 EX33 = Esperox 33                                                 

These formulations were polymerized and cured in the manner describedabove for Comparative Example A and Example 1 to provide for opticallyclear xerogel polymer compositions.

Afterwards, the xerogel polymers of Examples 2 and 3 were subjected tohydrolysis using a 5% solution of ammonium hydroxide which resulted bothin removal of the blocking groups (via solvolysis) and hydration of thepolymer composition. The resulting compositions were both opticallyclear and had the physical properties set forth in Table IV below:

                  TABLE IV                                                        ______________________________________                                                                                 Linear                               Ex.                                      Ex-                                  No.  Modulus.sup.A                                                                           Tens..sup.B                                                                             % Elong.                                                                             EWC      pansion                              ______________________________________                                        2     4.4 ± 1.1                                                                            4.1 ± 1.6                                                                           117 ± 28                                                                          64.4 ± 0.9%                                                                         22.2%                                3    12.5 ± 1.7                                                                           14.8 ± 6.7                                                                           140 ± 40                                                                          51.2 ± 0.7%                                                                          5.5%                                ______________________________________                                         A = in Mdynes/cm.sup.2                                                        B = in Mdynes/cm.sup.2                                                   

In both cases, the percent of linear expansion was maintained to lessthan 25% evidencing a degree of control of expansion arising fromhydration. Example 3, in particular, exemplifies a polymer compositionhaving approximately 50% water which undergoes minimal expansion duringhydration.

Accordingly, by selecting the removable blocking groups relative to theamount of water to be absorbed, it is possible to provide for a polymercomposition having little dimensional change during hydration.

EXAMPLES 4-21

The following examples are examples of optically clear polymercompositions, both as the xerogel and the hydrogel, within the scope ofthis invention. These polymer compositions were prepared in the mannerdescribed above and hydrated in a manner similar to that also describedabove. The formulations employed to prepare these polymer compositionsare described in Table V below:

                  TABLE V                                                         ______________________________________                                        HCEGMA.sup.5   MMA/CAB.sup.6                                                                            BPAGMA.sup.7                                                                            EX33.sup.8                                ______________________________________                                        Example 4                                                                             94         8          0.5     0.4 wt %                                Example 5                                                                             97         8          0.5     0.4 wt %                                Example 6                                                                             94         8          1.0     0.4 wt %                                Example 7                                                                             97         8          1.0     0.4 wt %                                Example 8                                                                             94         12         0.5     0.4 wt %                                Example 9                                                                             97         12         0.5     0.4 wt %                                Example 10                                                                            94         12         1.0     0.4 wt %                                Example 11                                                                            97         12         1.0     0.4 wt %                                Example 12                                                                            96         11         0.4     0.4 wt %                                Example 13                                                                            98         11         0.4     0.4 wt %                                Example 14                                                                            96         13         0.4     0.4 wt %                                Example 15                                                                            98         13         0.4     0.4 wt %                                Example 16                                                                            96         11         0.4     0.4 wt %                                Example 17                                                                            98         11         0.4     0.4 wt %                                Example 18                                                                            96         13         0.4     0.4 wt %                                Example 19                                                                            98         13         0.4     0.4 wt %                                Example 20                                                                            97         12         0.4     0.4 wt %                                Example 21                                                                            96         11         0.4     0.4 wt %                                ______________________________________                                         .sup.5 HCEGMA = ditrichloroacetate ester of glyceryl methacrylate (stored     at -5° C.)                                                             .sup.6 MMA/CAB = 30% wt:wt cellulose acetate butyrate in methyl               methacrylate                                                                  .sup.7 BPAGMA = bisphenol-A 2hydroxypropyl dimethacrylate (1:2 wt:wt          BPAGMA in DMSO)                                                               .sup.8 EX33 = Esperox 33                                                 

In Examples 4-21, HCEGMA, MMA/CAB and BPAGMA amounts are all reported inparts by weight.

EXAMPLE 22

The purpose of this example is to illustrate the enhancement in surfacewettability of molded ophthalmic devices (contact lenses) made via themethods of this invention as compared to conventional prior art methods.Specifically, when polymerization of the monomer mix is conducted in apolypropylene mold, the hydrophobic nature of the mold tends to orientthe molecules during polymerization such that the resulting polymersurface contains a more hydrophobic nature than the interior of thepolymer.

This difference can be quantified by comparing the contact angle of thesurface of the polymer to that of a surface formed by lathing thepolymer such that the interior of the polymer is exposed. Typically,when the hydroxyl groups of the monomer are not blocked prior topolymerization, the resulting polymer composition will have asignificant increase in the contact angle of the surface formed duringpolymerization as opposed to the contact angle of a surface formed afterpolymerization by lathing. The increase in contact angle corresponds toa reduction in surface wettability.

In the present case, a polymer composition formed in the mannerdescribed above was tested for its contact angle for both the surfaceformed during polymerization as opposed to the contact angle of asurface formed after polymerization by lathing. In both cases, thecontact angle was 40°±2 evidencing that there was no reduction insurface wettability between the surface formed during polymerization andthe interior of the polymer. Without being limited to any theory, it isbelieved that the blocking groups employed on the hydroxyl groups ofthis invention alter the hydrophilic nature of the monomer to a morehydrophobic nature thereby permitting orientation of these groups on thesurface of the polymer. After polymer formation, the removal of theseblocking groups exposes hydroxyl groups on the surface of the polymer.In any event, the enhanced surface wettability is a beneficial attributeof the polymers of this invention.

By following the procedures set forth above, other optically clearpolymer compositions containing an interpenetrant and hydroxyl groupscan be prepared merely by substitution of an appropriate reagent for thereagent recited in the examples above. For example, a polymercomposition employing EGDMA can be prepared as above merely bysubstituting the BPAGNA cross-linker with the EGDMA cross-linker. Insuch a case, 0.0355 grams of the EGDMA can replace 0.274 grams of theBPAGMA/DMSO cross-linker. Other substitutions can be readily done whichsubstitutions are well within the skill of the art.

What is claimed is:
 1. An optically clear xerogel polymer compositioncomprising:a polymer comprising hydroxyl functional groups blocked witha removable blocking group, and at least about 1.5 weight percent of aninterpenetrant based on the total weight of the xerogel polymercomposition wherein said composition has a sufficient optical clarity topermit the passage of at least 80% of visible light through a 0.1millimeter (mm) thick sample of the composition.
 2. The polymercomposition according to claim 1 wherein said composition iscross-linked.
 3. The polymer composition according to claim 1 whereinthe polymer composition, after deblocking and hydration, has a watercontent of from about 35 to about 70 weight percent water based on thetotal weight of the hydrated hydrogel polymer composition and a modulusof at least about 2 Mdynes/cm².
 4. The xerogel polymer compositionaccording to claim 1 wherein said composition comprises from at leastabout 5 weight percent to about 60 weight percent of an interpenetrant.5. The xerogel polymer composition according to claim 1 wherein saidremovable blocking groups are selected from the group consisting ofbenzyl, benzoyl, t-butylbiphenylsilyl and acyl and haloacyl blockinggroups of from 2 to 8 carbon atoms.
 6. The xerogel polymer compositionaccording to claim 1 wherein said composition is sufficiently opticallyclear to permit the passage of at least 90% of visible light through a0.1 mm thick sample of the composition.
 7. An optically clearcross-linked xerogel polymer composition comprising the reaction productof:from about 70 to about 95 weight percent of di-trichloroacetate esterof glyceryl methacrylate hydroxyl functional groups based on the totalweight of the composition, from about 1.5 to about 30 weight percent ofcellulose acetate butyrate based on the total weight of the composition,and from about 0.1 to about 30 weight percent of a cross-linking agentbased on the total weight of the composition.
 8. A contact lenscomprising a polymer composition according to claim
 1. 9. A method forthe preparation of an optically clear xerogel polymer compositioncomprising a polymer comprising hydroxyl functionalities which hydroxylfunctionalities are blocked with removable blocking groups, and at leastabout 1.5 weight percent of an interpenetrant based on the total weightof the xerogel polymer composition wherein the polymer composition hassufficient optical clarity to permit the passage of at least 80% ofvisible light through a 0.1 millimeter (mm) thick sample of thecomposition which method comprises:(a) selecting a monomer compositionwherein each component thereof comprises a reactive vinyl functionalityand at least one of the components of the composition comprises at leastone hydroxyl functional group; (b) blocking the hydroxyl functionalitieson each of the hydroxyl containing monomer components selected in (a)above with a removable blocking group; (c) combining said monomercomposition with at least 1.5 weight percent of an interpenetrant basedon the total weight of the composition; and (d) polymerizing thecomposition produced in (c) above to provide an optically clear xerogelpolymer composition.
 10. A method for the preparation of an opticallyclear hydrogel polymer composition comprising a polymer comprisinghydroxyl functionalities and at least about 1.5 weight percent of aninterpenetrant based on the total weight of the xerogel polymercomposition wherein the polymer composition has sufficient opticalclarity to permit the passage of at least 80% of visible light through a0.1 millimeter (mm) thick sample of the composition which methodcomprises:(a) selecting a monomer composition wherein each componentthereof comprises a reactive vinyl functionality and at least one of thecomponents of the composition comprises at least one hydroxyl functionalgroup; (b) blocking the hydroxyl functionalities on each of the hydroxylcontaining monomer components selected in (a) above with a removableblocking group; (c) combining said monomer composition with at least 1.5weight percent of an interpenetrant based on the total weight of thecomposition; (d) polymerizing the composition produced in (c) above toprovide an optically clear xerogel composition; (e) removing theblocking groups from said hydroxyl groups; and (f) hydrating thecomposition produced in (e) above.
 11. The method according to claim 10wherein the blocking groups on said monomer components are solvolyzableblocking groups.
 12. The method according to claim 11 wherein thesolvolyzable blocking groups are selected from the group consisting ofacyl and haloacyl blocking groups of from 2 to 8 carbon atoms.
 13. Themethod according to claim 12 wherein the blocking group is a haloacylblocking group of the formula X₃ CC(O)O-- wherein each X isindependently selected from the group consisting of fluoro and chloro.14. The method according to claim 10 wherein the blocking groups areselected to reduce the volume change in the polymer composition duringhydration.
 15. The method according to claim 10 wherein saidpolymerization procedure (d) is conducted in the presence of water or awater containing solvent.
 16. The method according to claim 10 whereinsaid interpenetrants comprise one or more polymerizable groups.